How flexible is alpha-actinin's rod domain?

Abstract

Alpha-actinin, an actin binding protein, plays a key role in cell migration, cross-links actin filaments in the Z-disk, and is a major component of contractile muscle apparatus. The flexibility of the molecule is critical to its function. The flexibility of various regions of the molecule, including the linker connecting central subunits is studied using constant force steered molecular dynamics simulations. The linker, whose structure has been a subject of debate, is predicted to be semi-flexible. The flexibility of the linker is compared to all possible segments of equal length throughout the molecule. The stretching profile of the molecule at different forces suggests that loops and regions adjacent to the loops are much more rigid than the helices in the protein. Amino acid composition analysis of most flexible and most rigid regions of the molecule reveals that the rigid regions are rich in Ser, Val and Ile whereas the flexible regions are rich in Ala, Leu and Glu.